Is MVD p.Arg91Trp (c.271C>T) pathogenic?

MVD p.Arg91Trp (c.271C>T) is classified Uncertain significance in MVD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.101); Ultra-rare (popmax 0.03%, amr).

How common is MVD p.Arg91Trp (c.271C>T) in the general population?

MVD p.Arg91Trp (c.271C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about MVD p.Arg91Trp (c.271C>T)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

MVD p.Arg91Trp

c.271C>T · VCV3400170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.72, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 11 kb · p 0.00014 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/59,998 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00465% 75/1,612,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)	0.00424%	23,595
African / African-American	0.004%	24,980
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,582

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MVD
Protein: p.Arg91Trp
Coding: c.271C>T
MANE Select: NM_002461
Type: single nucleotide variant
Location: chr16:88657568 (GRCh38)
Gene constraint: LOEUF 1.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.52 · 1 PDB

Full MVD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MVD p.Phe249Ser Pathogenic ★★ same type
MVD p.Thr120Met Uncertain significance ★★ ⚠ same type
MVD p.Arg78= Benign ★★ same type
MVD p.Lys368= Benign/Likely benign ★★ same type
MVD p.Pro77= Benign ★★ same type
MVD c.1013+1G>T Pathogenic ★ same type
MVD c.1014-1G>T Likely pathogenic ★ same type
MVD p.Asn292Ser Pathogenic ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mvd-p-arg91trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown